What is the recommended treatment with Eliquis (apixaban) for a patient with a history of non-valvular atrial fibrillation, deep vein thrombosis, or pulmonary embolism, considering their kidney function and other medical conditions?

Apixaban (Eliquis) Treatment Recommendations

Standard Dosing for Nonvalvular Atrial Fibrillation

For most patients with nonvalvular atrial fibrillation, the recommended dose is 5 mg orally twice daily, with dose reduction to 2.5 mg twice daily only when patients meet at least 2 of 3 specific criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

Dose Reduction Criteria

• Reduce to 2.5 mg twice daily when at least 2 of the following are present: 1
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL
• Do not reduce dose if only one criterion is met 2
• This dosing algorithm was validated in the ARISTOTLE trial, which demonstrated 21% reduction in stroke/systemic embolism (HR 0.79,95% CI 0.66-0.95) and 31% reduction in major bleeding compared to warfarin 2, 3

Renal Impairment Considerations

Moderate to Severe Renal Impairment (CrCl 15-30 mL/min)

• Standard dosing algorithm applies—use 5 mg twice daily unless dose reduction criteria are met 2
• Apixaban has only 27% renal clearance, making it safer than dabigatran (80% renal) or rivaroxaban (66% renal) in renal impairment 3
• NOACs including apixaban show superior efficacy to warfarin in CKD patients with CrCl 30-59 mL/min, with high-dose NOACs reducing stroke/systemic embolism (RR 0.79,95% CI 0.66-0.93) and all-cause death (RR 0.88,95% CI 0.78-0.99) 4

End-Stage Renal Disease on Hemodialysis

• Start with 5 mg twice daily 2, 3
• Reduce to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: different criteria than non-dialysis patients—only one criterion needed, not two) 2, 3
• Observational data from 25,523 dialysis patients showed apixaban had similar stroke prevention to warfarin (HR 0.88,95% CI 0.69-1.12) but significantly lower major bleeding risk (HR 0.72,95% CI 0.59-0.87, P<0.001) 4

Contraindications

• Do not use apixaban in patients with CrCl <15 mL/min who are not on dialysis 2, 1

Deep Vein Thrombosis and Pulmonary Embolism

Acute Treatment Phase

• 10 mg orally twice daily for the first 7 days 1
• After 7 days, reduce to 5 mg twice daily 1

Prevention of Recurrence

• After completing at least 6 months of treatment for DVT/PE, reduce to 2.5 mg twice daily for extended prophylaxis 1

Post-Surgical Prophylaxis

• Hip or knee replacement: 2.5 mg twice daily starting 12-24 hours after surgery 1
• Duration: 35 days for hip replacement, 12 days for knee replacement 1

Initiation and Switching Protocols

Starting Apixaban (No Loading Dose Required)

• Begin at appropriate dose based on indication and patient characteristics 2
• No bridging anticoagulation needed 2

Switching From Warfarin to Apixaban

• Discontinue warfarin 1
• Start apixaban when INR falls below 2.0 1
• No bridging therapy required 2

Switching From Apixaban to Warfarin

• Discontinue apixaban 1
• Begin both parenteral anticoagulant and warfarin at the time of next scheduled apixaban dose 1
• Continue parenteral anticoagulant until INR reaches therapeutic range 1
• Note: Apixaban affects INR measurements during transition 1

Switching Between DOACs

• Discontinue current DOAC 1
• Start apixaban at the time the next dose of previous DOAC would have been due 1

Perioperative Management

Elective Surgery or Invasive Procedures

• High/moderate bleeding risk procedures: Discontinue at least 48 hours prior 1
• Low bleeding risk procedures: Discontinue at least 24 hours prior 1
• Bridging anticoagulation during the 24-48 hour interruption is not generally required 1
• Restart as soon as adequate hemostasis is established 1

Cardioversion

• Apixaban is equivalent to warfarin for cardioversion safety 4
• Can use either conventional approach (3 weeks therapeutic anticoagulation pre-cardioversion) or TEE-guided approach with abbreviated anticoagulation 4
• NOACs vs warfarin in TEE-guided approach showed RR 0.33 (95% CI 0.06-1.68) for stroke/thromboembolism, indicating safety equivalence 4

Concurrent Antiplatelet Therapy

After Coronary Intervention

• Preferred strategy: Apixaban plus clopidogrel (without aspirin) after brief periprocedural period reduces bleeding while maintaining efficacy 2
• Clopidogrel is the P2Y12 inhibitor of choice when combined with apixaban 2

Stable Coronary Disease

• Apixaban monotherapy is appropriate—adding antiplatelet therapy increases bleeding without clear benefit 2

Monitoring Requirements

Renal Function Assessment

• Check before starting therapy 2
• Reassess at least annually 2, 1
• More frequent monitoring (every 3-6 months) if CrCl 30-50 mL/min or other risk factors for deterioration 2

Routine Coagulation Monitoring

• Not required 2
• Assess clinically for signs of bleeding or thromboembolism 2

Drug Interactions

Contraindicated Combinations (in patients on 5 mg twice daily)

• Avoid combined P-glycoprotein and strong CYP3A4 inhibitors: 3
  • Ketoconazole
  • Ritonavir
  • Itraconazole
• If combination necessary, reduce apixaban to 2.5 mg twice daily 3

Critical Safety Warnings

Premature Discontinuation Risk

• Discontinuing apixaban without alternative anticoagulation increases thrombotic event risk 1
• If stopping for reasons other than bleeding or completion of therapy, provide coverage with another anticoagulant 1

Neuraxial Anesthesia/Spinal Puncture

• Risk of spinal/epidural hematoma leading to permanent paralysis 1
• Risk factors include: indwelling epidural catheters, concurrent NSAIDs/antiplatelet agents, history of spinal trauma/surgery 1
• Monitor frequently for neurological impairment; urgent treatment necessary if compromise occurs 1
• Optimal timing between apixaban administration and neuraxial procedures is unknown 1

Missed Dose Management

• Take as soon as remembered on the same day 1
• Resume twice-daily schedule 1
• Do not double the dose 1
• Apixaban has a 12-hour half-life, and missed doses increase thromboembolic risk 2

Special Populations

Valvular Heart Disease

• Apixaban is approved for nonvalvular atrial fibrillation only 1, 5
• However, ARISTOTLE trial included 26.4% of patients with moderate/severe valvular disease (excluding mechanical valves and clinically significant mitral stenosis) 6
• No differential effect observed in patients with vs without valvular disease for efficacy or safety endpoints 6
• Contraindicated in patients with mechanical prosthetic heart valves or clinically significant mitral stenosis 5

Prior Stroke History

• Standard dosing criteria apply equally regardless of prior stroke 2
• Apixaban benefit is independent of prior stroke status 2